Detecting minute amounts of biochemical entities like biomolecules and small molecules is an important function both in research and in clinical diagnostics. Such detections are directly related to early diagnosis and monitoring of diseases such as cancer and diabetes. The development of biochemical sensors that are sensitive, robust, easy to build, and easy to use is of great significance because most sensitive platforms available today are generally cumbersome, costly, fragile, and difficult to make and operate.
Although there has been a deluge of biomarker development during the past decade using mass spectrometry and other highly sensitive analytical tools, in real practice it is imperative to reduce the cost and enhance the robustness of the sensing platforms in order to eventually transition many of these discoveries to the bedside.
Today, enzyme-linked immunosorbent assays (ELISA) in various forms are the predominant immunological diagnostic assays used in most clinical settings. Typical ELISAs perform sufficiently to address a broad range of both qualitative and quantitative needs. However, the ELISA platform requires significant laboratory facilities, equipment and expertise. The typical detection limits of ELISA are in the high picomolar (pM) to nanomolar (nM) range. Although the lowest achieved sensitivity reported in the literature of about 4 pM reaches beyond the benchmark level, the conditions and equipment required are not practical. Furthermore, standard ELISAs require extensive washing steps and quantification, which requires a spectrophotometer. These requirements render ELISA systems relatively difficult to scale both down in size and up in number and relatively difficult to transform into direct use for point-of-care diagnostics.
One class of scalable state-of-the-art biosensors developed using micromachining techniques is the class of nanomechanical cantilevers. These sensors have been used to detect DNA, proteins and antibodies at concentrations that range from 100s of pM to 100s of nM. Previously, sensors were developed to detect proteins at sub-pM levels using cantilevers in conjunction with aptamers. Cantilever sensors are fragile and, in general, difficult to use and integrate. Researchers have also developed micro and nanoelectronic bio sensors that detect entities by their charge. However, these bio sensors are ultimately limited by the screening of the target entities by the surrounding ions, particularly under high ionic conditions, as well as by the requirement of extremely precise optimization for integration and readout.
Therefore, there is an ever-increasing need for biochemical detection systems that are not only sensitive but also relatively simple, robust and versatile because such systems are more disposed to miniaturization, commercialization and wide usage.